The Journal of Experimental Medicine, Vol 116, 929-942,
©Copyright, 1962, by The Rockefeller Institute
DISSOCIATION OF THE BIOLOGICAL PROPERTIES OF BACTERIAL ENDOTOXIN BY CHEMICAL MODIFICATION OF THE MOLECULE
Henry H. Freedman Ph.D.1 and
Barnet M. Sultzer Ph.D.1
1 From the Princeton Laboratories, Inc., Princeton
The preparation and properties of three fractions isolated from the acetylation of endotoxin by acetic anhydride in the presence of anhydrous sodium acetate are described. One fraction is of primary interest for it allows the experimental dissociation of some of the myriad biological activities of the parent endotoxin. Pyrogenicity and acute toxicity are markedly reduced, and ability to confer tolerance to the lethality and pyrogenicity of homologous or heterologous endotoxins is equivalently diminished. In contrast, this acetylated derivative retains the ability to stimulate phagocytosis and, as shown in the following paper, to enhance non-specific host resistance to infection. Detoxification is reversible, the original toxicity and pyrogenicity being recovered following mild saponification.
The implications of the findings are discussed, and it is suggested that the observed dissociation of biological properties is explained neither by deacetylation of the derivative in vivo nor by the observable alteration of physical state in the gross.
Submitted on June 6, 1962
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